Nanoparticle probes and methods of making and use thereof

Abstract

Some embodiments relate to nanoparticle probes for the detection of disease states in a patient or for tissue engineering. In some embodiments, the nanoparticle probe comprises one or more slip bonds that bind to a cell surface structure. In some embodiments, the binding of the nanoparticle probe is selective. In some embodiments, the nanoparticle probe binds to cells having a certain maximum glycocalyx thickness.

What is claimed is: 
     
       1. A nanoparticle probe comprising:
 a nanoparticle base structure functionalized with a therapeutic agent, wherein the therapeutic agent is a growth factor; and 
 a slip bond moiety comprising a ligand for a glycocalyx of a cell; 
 a polymeric tether functionalized to the nanoparticle base structure and to an associative moiety, wherein said associative moiety comprises a ligand for a cell surface protein, a receptor, or a biomarker; and 
 wherein the associative moiety preferentially binds to the protein, the receptor, and the biomarker of the cell based on the thickness of a glycocalyx layer of the cell. 
 
     
     
       2. The nanoparticle probe of  claim 1  wherein the therapeutic agent is vascular endothelial growth factor (VEGF), angiopoietins, fibroblast growth factor (FGF) or combinations thereof. 
     
     
       3. The nanoparticle probe of  claim 1 , wherein the associative moiety binds irreversibly. 
     
     
       4. The nanoparticle probe of  claim 1  wherein the nanoparticle probe is functionalized with one or more dye or radio opaque agent for visualization. 
     
     
       5. The nanoparticle probe of  claim 1 , wherein the associative moiety comprises an oligonucleotide. 
     
     
       6. The nanoparticle probe of  claim 1  wherein the tether length is between 20-200 nm. 
     
     
       7. The nanoparticle probe of  claim 1  wherein the associative moiety penetrates the glycocalx. 
     
     
       8. The nanoparticle probe of  claim 1 , wherein the slip bond comprises one or more of a hyaluronan targeting motif, chondroitin sulfate targeting motif, dermatan sulfate targeting motif, heparan sulfate targeting motif, and/or combinations of the foregoing. 
     
     
       9. The nanoparticle probe of  claim 1 , wherein the nanoparticle base structure comprises poly(amidoamine) (PAMAM) dendrimers, gold, albumin, dendrimeric poly(l-lysine), dendrimeric polypropylenimine (PPI), Denkewalter-type PLL dendrimer, Tomalia-type PAMAM dendrimer, hydroxylated PAMAM dendrimer, Hult-type poly(ester) (bis-MPA) dendrimer, Majoral/Caminadetype phosphorous-based dendrimer, Simanek-type triazine based dendrimer, Jayaraman/Jain-type poly(propyletherimine) (PETIM) dendrimer, peptide dendrimer conjugate, or combinations thereof. 
     
     
       10. The nanoparticle probe of  claim 1 , wherein the nanoparticle probe self-assembles into a nucleation site for bone development. 
     
     
       11. A method of diagnosing a dysfunctional tissue in a patient comprising:
 administering the nanoparticle probe of  claim 1  to the patient; and 
 detecting the nanoparticle probe in the patient. 
 
     
     
       12. The method of  claim 11 , wherein the dysfunctional tissue of the patient is a bone, heart, kidney, liver, lung, intestine or pancreatic tissue. 
     
     
       13. The method of  claim 11 , wherein the dysfunctional tissue of the patient is bone with osteoporosis. 
     
     
       14. The method of  claim 11 , wherein the patient is in need of a bone graft. 
     
     
       15. The method of  claim 11 , wherein an increase in bone density is detected. 
     
     
       16. A method of treating a disease in a patient comprising:
 administering the nanoprobe of  claim 1  to the patient; and 
 detecting a change in tissue density in the patient. 
 
     
     
       17. The method of  claim 16  wherein an increase in vasculature, circulation, bone density and/or extra cellular matrix deposition is detected. 
     
     
       18. The nanoparticle probe of  claim 1 , wherein the associative moiety comprises sialyl Lewis X. 
     
     
       19. The nanoparticle probe of  claim 1 , wherein the associative moiety comprises one or more of RGD, scFv, or sdAb. 
     
     
       20. The nanoparticle probe of  claim 1 , wherein the slip bond moiety comprises a lectin. 
     
     
       21. The nanoparticle probe of  claim 1 , wherein the slip bond moiety comprises an antibody. 
     
     
       22. The nanoparticle probe of  claim 1 , wherein the nanoparticle base structure comprises DNA origami or RNA origami. 
     
     
       23. The nanoparticle probe of  claim 1 , wherein the nanoparticle base structure comprises a gold nanoparticle, an iron-oxide nanoparticle, colloidal gold, TNF-bound colloidal gold, or combinations thereof. 
     
     
       24. The nanoparticle probe of  claim 1 , wherein the nanoparticle base structure comprises albumin, polystyrene latex particles, PEG-PLL, PEG-PAMAM, PETIM-DG, PEG-PPI, or combinations thereof.